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含1个糖基转移酶8结构域的蛋白过表达通过介导PTPN6/JAK2/STAT3信号轴促进胃癌增殖并抑制凋亡。

Overexpression of Glycosyltransferase 8 Domain Containing 1 Promotes Gastric Cancer Proliferation and Inhibits Apoptosis via Mediating PTPN6/JAK2/STAT3 Signaling Axis.

作者信息

Sun Yingying, Zhang Wuqian, Cong Qunyou, Ge Yanli, Zhang Junjie, Wang Haiyang, Wang Zhe, Wang Zhirong

机构信息

Department of Gastroenterology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

Department of Laboratory Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

出版信息

Int J Med Sci. 2024 Nov 11;21(15):2943-2958. doi: 10.7150/ijms.102719. eCollection 2024.

Abstract

The mechanisms of gastric cancer (GC) occurrence and development are still unclear. Although glycosyltransferase 8 domain containing 1 (GLT8D1) has been implicated in GC, its specific role and molecular mechanisms in GC progression need to be further investigated. Tissue microarrays were used to detect the expression levels of GLT8D1 in 80 GC tissues and their corresponding non-tumor adjacent tissues. The correlations between the GLT8D1 expression level and clinicopathological characteristics were evaluated. A series of and functional experiments were performed to explore the role of GLT8D1 in GC progression. Combined with transcriptomic RNA sequencing (RNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), we delineated the potential mechanisms via experimental verification. Elevated expression of GLT8D1 in GC tissues was positively correlated with advanced clinical stages and poor prognosis. Konckdown of GLT8D1 significantly inhibited GC cell proliferation and induced apoptosis, whereas overexpression did the opposite. Further researches demonstrated that protein tyrosine phosphatase non-receptor type 6 (PTPN6), a downstream target of GLT8D1, has the capacity to modulate the activity of the JAK2/STAT3 signaling pathway. Our study indicated that GLT8D1 expression was upregulated in GC tissues and correlated with poor prognosis. We reveal a potential molecular mechanism by which GLT8D1 promotes GC progression.

摘要

胃癌(GC)发生和发展的机制仍不清楚。尽管含糖基转移酶8结构域1(GLT8D1)与胃癌有关,但其在胃癌进展中的具体作用和分子机制仍需进一步研究。使用组织芯片检测80例胃癌组织及其相应的癌旁非肿瘤组织中GLT8D1的表达水平。评估GLT8D1表达水平与临床病理特征之间的相关性。进行了一系列功能实验以探讨GLT8D1在胃癌进展中的作用。结合转录组RNA测序(RNA-seq)和加权基因共表达网络分析(WGCNA),我们通过实验验证描绘了潜在机制。胃癌组织中GLT8D1的表达升高与临床晚期和预后不良呈正相关。敲低GLT8D1可显著抑制胃癌细胞增殖并诱导凋亡,而过表达则相反。进一步研究表明,GLT8D1的下游靶点非受体型蛋白酪氨酸磷酸酶6(PTPN6)具有调节JAK2/STAT3信号通路活性的能力。我们的研究表明,GLT8D1在胃癌组织中的表达上调且与预后不良相关。我们揭示了GLT8D1促进胃癌进展的潜在分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e1/11610327/c85c111f9644/ijmsv21p2943g001.jpg

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